Alport syndrome is an inherited, X-linked progressive nephritis that culminates in end-stage renal disease, and is usually accompanied by a severe, sensorineural hearing loss. Dr. Gregory and his colleagues have established that most cases of Alport syndrome are caused by defects in a gene designated COL4A5, a gene located on the X chromosome that encodes a type of collagen critical for normal function of the kidney and the ear. Dr. Gregory's current studies are aimed at determining how specific mutations of the COL4A5 gene are responsible for the clinical features of Alport syndrome, which can vary widely from family to family. Dr. Gregory's group is also seeking evidence for mutations in other collagen genes in Alport syndrome families who do not demonstrate COL4A5 mutations.